Hiroaki Akamatsu1, Yasuhiro Koh2, Hirotsugu Kenmotsu3, Tateaki Naito3, Masakuni Serizawa4, Madoka Kimura5, Keita Mori6, Hisao Imai3, Akira Ono3, Takehito Shukuya7, Tetsuhiko Taira3, Haruyasu Murakami3, Yasuhisa Ohde8, Masahiro Endo9, Takashi Nakajima10, Toshiaki Takahashi3, Nobuyuki Yamamoto11. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama. 2. Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka. Electronic address: ykoh@wakayama-med.ac.jp. 3. Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo. 4. Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka. 5. Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka. 6. Clinical Trial Management Department, Shizuoka Cancer Center, Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka. 7. Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Department of Respiratory Medicine, Juntendo University, Tokyo. 8. Division of Thoracic Surgery, Nagaizumi-cho Sunto-gun, Shizuoka, Japan. 9. Division of Diagnostic Radiology, Nagaizumi-cho Sunto-gun, Shizuoka, Japan. 10. Division of Diagnostic Pathology, Shizuoka Cancer Center, Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka, Japan. 11. Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama.
Abstract
INTRODUCTION: Pleural effusion is frequently observed in patients with advanced lung cancer. Although effusion can be obtained less invasively and repeatedly, its use in multiplexed molecular profiling has not been fully investigated. METHODS: Between July 2011 and April 2013, pleural effusion samples were obtained from patients with lung cancer at Shizuoka Cancer Center. They were analyzed for EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 mutations, EGFR, MET, FGFR1, FGFR2, and PIK3CA amplifications, and ALK, ROS1, and RET fusion genes using pyrosequensing and/or capillary electrophoresis, quantitative reverse-transcriptase polymerase chain reaction, and reverse-transcriptase polymerase chain reaction, respectively. RESULTS: One hundred and two samples from 84 patients were analyzed. Adenocarcinoma was the most common histological subtype (82%). Genetic abnormalities were detected in 42% of patients. The most common abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%), KRAS mutation, and EGFR amplification (4%, each). Concordance rates between pleural effusion and matched formalin-fixed, paraffin-embedded samples were 88%. Among 11 patients who provided samples at multiple time points, changes in molecular profile over the course of treatment were observed in five patients. CONCLUSIONS: The use of pleural effusion for multiplexed molecular testing and real-time monitoring in lung cancer was demonstrated.
INTRODUCTION:Pleural effusion is frequently observed in patients with advanced lung cancer. Although effusion can be obtained less invasively and repeatedly, its use in multiplexed molecular profiling has not been fully investigated. METHODS: Between July 2011 and April 2013, pleural effusion samples were obtained from patients with lung cancer at Shizuoka Cancer Center. They were analyzed for EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 mutations, EGFR, MET, FGFR1, FGFR2, and PIK3CA amplifications, and ALK, ROS1, and RET fusion genes using pyrosequensing and/or capillary electrophoresis, quantitative reverse-transcriptase polymerase chain reaction, and reverse-transcriptase polymerase chain reaction, respectively. RESULTS: One hundred and two samples from 84 patients were analyzed. Adenocarcinoma was the most common histological subtype (82%). Genetic abnormalities were detected in 42% of patients. The most common abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%), KRAS mutation, and EGFR amplification (4%, each). Concordance rates between pleural effusion and matched formalin-fixed, paraffin-embedded samples were 88%. Among 11 patients who provided samples at multiple time points, changes in molecular profile over the course of treatment were observed in five patients. CONCLUSIONS: The use of pleural effusion for multiplexed molecular testing and real-time monitoring in lung cancer was demonstrated.